Prophylactic effect and mechanism of p-coumaric acid against hypoxic cerebral edema in mice

Respir Physiol Neurobiol. 2019 Feb:260:95-104. doi: 10.1016/j.resp.2018.11.004. Epub 2018 Nov 14.

Abstract

Our previous study found that the anti-hypoxia effect of Tibetan turnip (Brassica rapa ssp. rapa) is directly related to its p-Coumaric acid (CA) and glucoside (pCoumaric acid-beta-d-glucopyranoside, CAG) contents. The present study aimed to investigate the role and mechanism of CA against hypoxic cerebral edema. Male mice were randomly divided into one normoxia group and three hypoxia groups, which were gavaged with sterilized water, CA, or dexamethasone, respectively, once daily for 4 days. The mice were then exposed to normoxia or hypoxia (9.5% O2) for 24 h. The results showed that the brain water content (BWC) and blood-brain-barrier permeability were significantly lower in the CA treatment group than in the hypoxia vehicle group. Mice in the CA treatment group showed good blood-brain-barrier integrity; increased Na+-K+-ATPase activity and mitochondrial membrane potential; decreased oxidative stress and inflammation; and increased occludin protein levels. Prophylactic administration of CA and dexamethasone exerted similar effects against hypoxic cerebral edema. The mechanism involved improving the integrity of the blood-brain-barrier, and inhibiting oxidative stress and inflammation.

Keywords: Acute normobaric hypoxia; Cerebral edema; Inflammation; Occludin; Oxidative stress; p-Coumaric acid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / therapeutic use*
  • Blood-Brain Barrier / drug effects
  • Brain Edema / etiology*
  • Brain Edema / prevention & control*
  • Catalase / metabolism
  • Coumaric Acids
  • Cytokines
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Encephalitis / etiology
  • Encephalitis / prevention & control
  • Glutathione / metabolism
  • Glutathione Peroxidase / metabolism
  • Hypoxia / complications*
  • Male
  • Membrane Potential, Mitochondrial / drug effects
  • Mice
  • Mice, Inbred ICR
  • Occludin / metabolism
  • Oxidative Stress
  • Propionates / therapeutic use*
  • Sodium-Potassium-Exchanging ATPase / metabolism

Substances

  • Antioxidants
  • Coumaric Acids
  • Cytokines
  • Occludin
  • Propionates
  • Catalase
  • Glutathione Peroxidase
  • Sodium-Potassium-Exchanging ATPase
  • Glutathione
  • p-coumaric acid